In this application for competing renewal, we request five years of modular funding to continue our aim to complete the first adequately powered, placebo (PBO) controlled randomized clinical trial evaluating the efficacy of continuation phase cognitive therapy (C-CT) and fluoxetine (FLX) in outpatients with recurrent Major Depressive Disorder (MOD) who are at high risk for relapse. The trial is being conducted at The University of Texas Southwestern Medical Center and The University of Pittsburgh School of Medicine. "Higher risk" is defined by incomplete remission during the final weeks of acute phase CT, while "lower risk" is defined as a complete and stable remission. This trial has great public health significance because it will help clinicians to identify those patients at greatest risk for relapse who warrant longer courses of treatment and can produce greater choices for patients in relapse prevention. Such empirically-based decision rules could lower the cost of care by providing enough treatment for a depressive episode without either "over- treating" patients at lower risk or "under-treating" those patients at higher risk. This study is the first to evaluate continuation phase pharmacotherapy (FLX) after incomplete remission with acute phase CT. Further, the pharmacotherapy group will permit tests of mode-specific vs. non-specific therapeutic activity. Dependent variables measure response, relapse, recurrence, remission, and recovery. Blind evaluations and survival analyses are planned. Based on results of an interim analysis requested by the IRQ and on current relapse rates (i.e., C-CT 10%;FLX 22 %;and PBO 22%), the power analysis showed that a total of 120 newly randomized subjects are needed to compare the efficacy C-CT vs. FLX. This application proposes to randomize 90 patients and continue as an unbalanced 3-arm trial. (In Year 7-11 only 5% of patients will be randomized to PBO to maximize the statistical power for comparison of C-CT and FLX, without undermining the original design or changing patient or staff expectations). During this renewal, 180 of the required new patients will be enrolled into acute phase cognitive therapy (A-CT). At the end of this project period accrual across all funding will total: A-CT n=665 of the required patients and randomization will equal 107 of the required patients in C-CT;of the required 107 in FLX;and 53 of the patients required for PBO.